Carvalho AF, Van Bockstaele E (2010) Defining the role of norepinephrine in cannabinoid-induced aversion and anxiety. Neuroscience 2010 Abstracts 833.3. Society for Neuroscience, San Diego, CA.
Summary: In the central nervous system, cannabinoids have been shown to regulate neurotransmitter release, control the hypothalamic-pituitary-adrenal axis and impact several physiological systems, such as food intake, pain and emotion perception. Manipulation of the cannabinoid system using exogenous compounds has been explored as a potential therapeutic for several disorders; however some severe side effects have been reported. Understanding the neural circuits and neurochemical substrates impacted by cannabinoids will provide a better means of gauging their actions within the central nervous system that may contribute to the expression of unwanted side effects. Previous work from our lab had shown that the cannabinoid receptor (CBr) agonist WIN 55,212-2 is able to induce changes in noradrenergic transmission in limbic structures such as prefrontal cortex (PFC) and the nucleus accumbens (Acb). Moreover, we have previously reported that norepinephrine in the nucleus accumbens (Acb) is critical for WIN 55,212-2-induced aversion, as measured by the place conditioning paradigm. In the present study, we further explore the role of norepinephrine in cannabinoid-induced behaviors. More specifically, we investigate whether norepinephrine in the limbic forebrain of rats is important for the anxiety induced by WIN 55,212-2 (3.0 mg/kg, i.p.). Lesion of noradrenergic neurons in the Acb and bed nucleus of the stria terminalis (BNST) was achieved by the intracerebral injection of the toxin saporin conjugated with an antibody that recognizes the enzyme dopamine-beta-hydroxylase (DBH). This toxin yields a specific lesion of noradrenergic neurons. The anxiogenic effects of WIN 55,212-2 were then measured in the elevated zero maze. The results show that depletion of noradrenergic innervation of the Acb and BNST did not reduce the anxiogenic properties of WIN 55,212-2. These results, together with our previous findings, suggest that the anxiogenic and aversive properties of the CBr agonist WIN 55,212-2 are differentially regulated, with the aversive effects being dependent on noradrenergic transmission within the Acb and the anxiogenic effects being regulated by a, yet to be determined, alternative mechanism/circuit.
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